生育力与早期胚胎发育毒性试验中雄性大鼠阳性模型的建立

Positive modeling study on fertility and early embryo developmental toxicity in SD male rat

目的:探讨生育力与早期胚胎发育毒性试验中,SD雄鼠交配前的环磷酰胺给药方法,以建立阳性对照模型。方法:SD大鼠按体质量随机分为3组,分别为溶剂对照组、环磷酰胺I组(100mg/kg)、环磷酰胺II组(20mg/kg);环磷酰胺I组和II组分别腹腔注射给予环磷酰胺1次和5次,溶剂对照组给予等量的生理盐水;雄鼠于首次给药后63d开始交配,交配成功后当天检测阴茎勃起功能,随后处死,进行精子活动度和数量检测,腹主动脉采血后检测双氢睾酮、雌二醇和睾酮激素水平,称量睾丸、附睾、包皮腺、前列腺、精囊腺、提肛肌等的质量并计算脏器系数。结果:2个环磷酰胺组雄鼠主要表现为可逆性脱毛。与溶剂对照组比较,体质量和摄食量均明显降低(P<0.05或0.01);雄鼠附属生殖器官质量降低(P<0.01),阴茎勃起潜伏期明显延长(P<0.01),附睾尾精子计数、Ⅰ和Ⅱ级活动精子数及精子活率降低,精子畸形率明显增高(P<0.05或0.01),但激素水平未见明显异常。结论:给予环磷酰胺对于雄性大鼠的生育力产生明显影响,两种给药方式均可建立生育力与早期胚胎发育毒性试验阳性模型。

OBJECTIVE： To establish male rat fertility and early embryo developmental toxicity test （I section） positive control model, cyclophosphamide was given by i.p. before mating. METHODS： Male Sprague-Dawley rats were divided into control group, cyclophosphamide I and eyelophosphamide II groups. Cyclophosphamide groups were given intraperitoneally on day 1 of 9 weeks （100 mg/kg） and the first 5 days of 9 weeks （20 mg/kg）. Male rats were sacrificed after mating, the parameters were observed and tested. RESULTS： Positive groups male animals showed reversible depilatory. Animal body weight and then food consumption were decreased significantly when compared with the control group, although no significant differences in the hormone level were found. Weights of auxiliary reproductive organ were significantly decreased, time for penis erection was significantly longer, sperm count and sperm activity ratio were decreased, and sperm malformation rate was increased significantly. CONCLUSION： Cyclophosphamide exeited significant effects on male fertility, and both treatment methods could be used to establish positive fertility and early embryo developmental toxicity test model.